tbuckley/cabot-search huggingface dataset:
A Longitudinal Study to Evaluate Biomarkers in Brain Tumour Patients
Authors: Ellen Whiteside
Journal: Neuro-Oncology (2022)

Abstract AIMS To monitor brain tumour patient blood for predictive and prognostic biomarkers, in a prospective longitudinal study. Continuing the research of Dr. Abel the results may be used to predict tumour recurrence and progression from low- to high-grade. The results may be useful in the clinical management of malignant glioma patients. METHOD A patented panel of biomarkers will be investigated using FFPE tissue and blood components from adult brain tumour patients in the North West region. Biomarker expression will be analysed in different molecular sub-types of glioma, grouped by IDH and methylation status. An evaluation will be conducted to determine if reference ranges can be created to distinguish between high-and low-grade tumours. Spectroscopic analysis of blood samples will be tested to determine if cancerous and non-cancerous can be differentiated from each other. There will be testing of selected miRNA’s for up and down regulation patterns. Sample Intervals: Initial diagnosis, 24 hours post-surgery, pre-therapy, post-radiotherapy, after adjuvant therapy, at 3 then 6 monthly post therapy, at recurrence or suspected recurrence and at intervals during further therapy and follow up. RESULTS There are no results to report at this point in the study time line. Testing to start in April 2022. CONCLUSION The potential impact of research would work towards lower patient risk and less invasive procedures. If used as a screening tool could allow high NHS savings. There could be an impact on patient experience and survival if recurrence could be detected [NICE guideline NG99] recommendation for research.
Brain Tumour Diagnosis and Relationships Among Patients: A Social Science Perspective on Changing Tumour Classification
Authors: Henry Llewellyn, Louise Dulley, Paul Higgs, David Louis, Elizabeth Sampson, Paddy Stone, Louis Thorne
Journal: Neuro-Oncology (2022)

Abstract AIMS Peer-to-peer relationships between people with a brain tumour are critical to how they cope with illness. These are often premised on shared diagnoses. However, as molecular genetic/epigenetic markers revise tumour classification, the terms of such relationships could also change. We explore these relationships and the potential repercussions for patients whose diagnoses are revised according to new tumour classification. METHOD We draw on two UK-based ethnographic studies of brain tumour care. The first examined how patients navigated complex healthcare systems (2014-2016); the second explored changing classification and personalised medicine (2020-2021). Both involved repeated qualitative interviews with patients, families, clinicians and classification experts, and observations of routine care. Here, we focus on interviews and observations with patients (N=29). RESULTS Patients described how peer-to-peer relationships helped them understand their condition, envision their futures, find solidarity, navigate medical decisions, and access non-standard treatments. Many described the importance of finding people who shared their diagnosis. One patient, whose diagnosis was revised to a less aggressive tumour years after being first diagnosed, described how a radical change in prognosis challenged her relationships with peers, and contributed to significant survivor guilt as she outlived them. CONCLUSION Our findings confirm the importance of peer-to-peer relationships for patients. They suggest how changing tumour classification could have significant unforeseen social and psychological impacts for patients, including survivor guilt, by changing the nature of such relationships. We speculate that this will become more common in an era of personalised medicine and when breakthroughs in cancer understanding are more rapidly integrated in routine care.
The Role of miRNAs in Gliomas in Response to Hypoxia
Authors: Louise Smith, Sajib Chakraborty, Anbarasu Lourdusamy, Alan McIntyre, Stuart Smith
Journal: Neuro-Oncology (2022)

Abstract AIMS Identifying significant miRNAs that are either under or overexpressed in hypoxia compared to normoxia in glioma cells. Further exploring the effect and role of hypoxia on miR-92a-3p and miR-149-5p in gliomas in apoptotic and cellular senescence pathways. METHOD A range of glioma cells were used for screening, including primary cell lines: GIN28 and GIN31; low-grade cell lines: LGG19 and LGG24; a paediatric cell line: SF188 and a commercially available glioblastoma cell line U87. These cells were cultured at both 1% (hypoxia) and 20% (normoxia) oxygen levels. Screening of miRNAs was achieved by quantitative polymerase chain reaction (qPCR) using miRNA specific primers. Knockdowns/in were achieved by transfecting with miR-92a-3p and miR-149-5p mimics and inhibitors. Caspase-glo assay was used to assess the effect of hypoxia on apoptosis. RESULTS A range of miRNAs were differentially expressed in hypoxia in a range of glioma cell lines. miRNA 92a-3p and miR-149-5p were found to be downregulated and upregulated respectively in primary gliomablastoma cells in hypoxia compared to normoxia. These particular miRNAs are also found to have multiple targets in apoptosis and cellular senescence. CONCLUSION The screening of 90 miRNAs among the different categories of gliomas highlighted multiple miRNAs that were significant in hypoxia compared to normoxia. Using primary cell lines have identified hypoxia-affected miRNAs in glioblastomas. This discovery will increase our knowledge and understanding of the hypoxia effect on miRNAs which may aid and direct targeted therapy to conquer hypoxia in glioblastomas.
Pro-drug Nanoparticle Loaded Supramolecular Hydrogels for Drug Delivery to IDH1 Wild-Type Glioblastoma
Authors: Robert Cavanagh, Saif Baquain, Cameron Alexander, Oren Scherman, Ruman Rahman
Journal: Neuro-Oncology (2022)

Abstract AIMS A hyaluronic acid-based hydrogel with mechanical properties comparable to human brain tissue is being investigated as an implantable drug-delivery vehicle for post-surgical treatment of IDH1 wild-type glioblastoma (GBM). Hydrogels are to be loaded with polymeric pro-drug nanoparticles to enable controlled drug release and increased drug penetration through brain parenchyma for enhanced treatment of residual disease within and beyond the invasive margin. METHOD A panel of patient-derived glioblastoma cell lines resected from tumour core and invasive margin, have been used to generate tumour spheroids. Chemotherapeutic drug screening has been performed to select lead compounds for formulation and gel loading. Synergies of drug combinations have been studied for potential combination loading. Upcoming work will investigate nanoparticle internalisation, spheroid penetration and prodrug nanoparticle potency. Nanoparticle loaded hydrogels are then to be studied for validation of effective in vitro application. RESULTS Current results demonstrate that patient-derived cell lines can generate robust, reproducible tumour spheroids with diameters approx. 350-400 µm. Patient-to-patient differences in drug potencies were observed, with differences also noted between counterpart core and marginal cells from the same patients, illustrating the importance of using patient-derived cells and distinct regional cells to study heterogenous disease such as GBM. Drug combination experiments indicated synergy of topoisomerase I inhibitor (Irinotecan) with PARP inhibitor (Ola-parib). Interestingly, combination of PARP inhibition with topoisomerase II inhibitors (Doxorubicin, Etoposide) was found not synergistic. CONCLUSION Together, data gathered on single drug and drug-drug combinations will inform upcoming formulation and in vitro application of hydrogels planned, with eventual translation to pre-clinical in vivo models.
Stereotactic Radiosurgery for Brainstem Metastases
Authors: Mitchell Hickman, Helen Benghiat, Sara Meade, Geoff Hayes, Andrew Hartley, Paul Sanghera
Journal: Neuro-Oncology (2022)

Abstract AIMS Limited data exists on outcomes following SRS for brainstem metastases (BSM). The purpose of this audit was to explore the use of SRS using Cyberknife for BSM at a single centre; reporting rates of toxicity and survival outcomes. METHOD Patients undergoing SRS for BSM from 2013 to 2021 were identified from a prospective database. Clinical characteristics were collected including; gender, age, histology and KPS. The use of previous WBRT, the volume and the dose delivered to the BSM were also recorded. All target volumes were peer reviewed by a neuro-radiologist. RESULTS 41 patients with a BSM were identified. The median age was 62 years (range 35-78). Histology was lung 15 (36.6%), breast 13 (31.7%) and other 13(31.7%). The median brainstem target volume was 0.36cc (range 0.01 – 5.63cc). 32 patients had single fraction (dose range 14.5 to 18Gy) and 9 patients had 3 fractions (dose range 17-24Gy). 7 patients had previous WBRT. Median overall survival was 242 days (range 19-1213). A radiological response or stable disease was seen in 26 out of 30 patients with post SRS imaging available for review. 2 patients developed a 6th nerve palsy. 12 patients required a prolonged course of dexamethasone. No statistically significant relationship was observed between patient age, brainstem lesion size or fractionation and the need for prolonged use of dexamethasone but there was a trend with lung cancer patients requiring prolonged dexamethasone (p=0.06). CONCLUSION Brainstem SRS is viable option with an acceptable late toxicity profile. Updated information on survival and local control will be presented.
Identifying Enhancing Tumour Without Contrast-Enhanced Imaging
Authors: James Ruﬄe, Samia Mohinta, Robert Gray, Harpreet Hyare, Parashkev Nachev
Journal: Neuro-Oncology (2022)

Abstract AIMS Brain tumours are heterogenous entities comprising multiple broad tissue sub-types when imaged with MRI. Delineating the enhancing tumour component is vital for neuro-oncological therapeutic planning, to-date only demonstrable with contrast-enhanced imaging. But not all patients can undergo this necessary contrast-enhanced acquisition, whether due to allergy, renal impairment, or scanning acquisition parameters. We therefore evaluated how well fully convolutional deep learning models identify a patient’s enhancing tumour when contrast-enhanced imaging was not available. METHOD We constructed a suite of deep-learning models to segment brain tumours when contrast-enhanced imaging was missing. Specifically, we developed all possible combinations of other structural sequences being provided, including T1-weighted, T2-weighted and FLAIR. Models were trained and tested with five-fold cross-validation on the 2021 BraTS-RSNA glioma population of 1251 patients, with additional out-of-sample validation with neuroradiologist hand-labelled lesions from our own centre. RESULTS Models missing post-contrast imaging still achieved a Dice coefficient for the whole tumour of 0.942. Model performances for identifying enhancing-tumour – despite no contrast-enhanced imaging being provided to the model – ranged from Dice coefficients of 0.759 (single sequence model) to 0.790 (three sequence T1 + T2 + FLAIR model). Moreover, models lacking contrast-enhanced imaging still robustly quantified the volume of enhancing tumour (R2 range 0.953-0.976). CONCLUSION Models missing contrast-enhanced imaging still identify both whole lesions and enhancing tumour components, and accurately quantifying the enhancing volumetric burden. These models provide opportunity for lesion detection in patients or clinical situations in which contrast-enhanced imaging cannot be acquired, and challenge the current nosology of defining ‘enhancing tumour’.
Low Grade Glioma - A COVID Low Surgical Priority?
Authors: William White, George Rudd, Hesham Zaki, Fiona McKevitt, Charles Romanowski, Shungu Ushewokunze
Journal: Neuro-Oncology (2022)

Abstract AIMS During the COVID pandemic (March 2020) SBNS published guidance advising that low grade gliomas (LGG) should be categorised as “low surgical priority”, therefore surgery could be delayed by six months. Aims: (1) Examine the effect of the COVID pandemic on the time taken from neuro-oncology MDT discussion to surgery in presumed LGG. (2) Investigate the proportion of presumed LGG receiving an integrated diagnosis of high grade glioma (HGG) before and during the COVID pandemic. METHOD Retrospective case note analysis of patients with presumed LGG including radiological and histopathological reports. Population split into two groups – Group A pre-pandemic (March 2019-2020) and Group B mid-pandemic (March-December 2020). RESULTS Forty-three patients (30M, 13F) with presumed LGG were identified – 23/43 in Group A and 20/43 in Group B. Mean age was 45 years (26-77y). Twenty-two patients (Group A 12/23 (52%) &amp; Group B 10/20 (50%)) had no radiological features of transformation. Mean number of days between discussion and surgery was 32 (2-96 days, SD=28) for group A and 98 (6-286 days, SD=92) for group B (p=.006: [95% CI: 21-110]). Fifteen patients in each group (65% v 75%) had an integrated diagnosis of HGG (p=.486). Of the patients with no radiological features of transformation 6 (50%) had a HGG in Group A and 7 (70%) in Group B (p=.342). CONCLUSION During the COVID pandemic patients with presumed LGG had their surgical management significantly delayed, with an increase in the proportion who were diagnosed with HGG. Presumed LGG patients should have higher surgical priority even when resources are constrained.
Need for standardized vancomycin dosing for coagulase-negative staphylococci in hospitalized infants
Authors: Eleanor J. Harvey, Diane Ashiru-Oredope, Louise F. Hill, Alicia Demirjian, Karthik Paranthaman, Elita Jauneikaite, Yu Wan, Russell Hope, Andrew Robb, Louise Thorn, Paul Fleming, Bruno Pichon, Derren Ready, Mustafa Elsayed, Heather Felgate, Ginny Moore, Santosh Pattnayak, Sakina Ali, Ted Gasiorowski, Timothy Watts, Louise Wooster, Vicky Payne, Colin Brown, Alleyna Claxton, Christina Kortsalioudaki, Mitul Patel, Nabeela Mughal, Olga Moncayo, Sujoy Banerjee, Liz McKechnie, Rashmi Gandhi, Rhys DCosta, Minesh Khashu, Natasha Ratnaraja, Kavita Sethi, Simon Drysdale, Bharat Patel
Journal: Clinical Microbiology and Infection (2022)
Corrigendum to “Chemically-induced osteogenic cells for bone tissue engineering and disease modeling” [Biomaterials 289 (2022) 121792]
Authors: Ji-Young Yoon, Nandin Mandakhbayar, Jeongeun Hyun, Dong Suk Yoon, Kapil D. Patel, Keunsoo Kang, Hosup Shim, Hae-Hyoung Lee, Jung-Hwan Lee, Kam W. Leong, Hae-Won Kim
Journal: Biomaterials (2022)
The Radiologist as a Consultant
Authors: Leonard N. Green
Journal: JAMA (1982)

<h3>To the Editor.—</h3> The following is in response to the view of Marc J. Homer, MD (1981;246:2581), that the radiologist should be considered as a consultant and to his comments in answer to Warren Bosley, MD (1982; 247:2233). It is commonly accepted practice in most hospitals that a consultant consults when he is invited to do so by the attending physician. This is true in the large majority of specialties and subspecialties, with one outstanding exception—radiology. When there is a necessity for imaging, most hospital rules require obligatory radiological "consultation." This is untrue of almost any other specialty area. If the radiologist wants to be considered a consultant similar to other consultants, why, then, should his opinion be regarded as obligatory and other specialists' opinions be dispensable? The attending physician should be given the same discretionary judgment regarding radiological consultation as he is given with other consultants. In Dr Homer's
Inheritance of Mental Defect.
Journal: JAMA (1931)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Integrated State of Subgenomic Fragments of Hepatitis B Virus DNA in Hepatocellular Carcinoma From Mainland China&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Yi-zhong Zhou, Janet S. Butel
 5, Pei-juan Li, Milton J. Finegold, Joseph L. Melnick
Journal: JNCI Journal of the National Cancer Institute (1987)

Hepatocellular carcinoma (HCC) samples from mainland China were examined for the presence and state of hepatitis B virus (HBV) DNA sequences. HBV DNA was detected by dot-blot hybridization in 13 of 17 cases of HCC from the Shanghai area and in three of six samples from Hangzhou. The HCC cases from Shanghai were then analyzed in more detail. Fifteen of the 17 patients had serologic evidence of past or present infection with HBV (with inadequate information available for the other two), and the 13 HCC samples positive for HBV DNA all came from serologically positive patients. Southern blot analysis showed that the HBV DNA sequences were always integrated in the HCC high-molecular-weight DNA; only one or two viral copies were present per tumor cell, and no common integration site was evident. Hybridization analyses using subgenomic probes of HBV DNA revealed that the tumors seldom retained an entire HBV genome. HBV S-region sequences were always present, X-region sequences were usually represented, and C-region sequences were rarely detectable in the virus-positive tumors. A fragment within the HBV DNA X-region, between nucleotides 1441 and 1526, was found to hybridize nonspecifically with cellular DNA; reported sequence data indicated that this fragment would contain approximately 70% guanine + cytosine. Histologic sections were prepared from some of the frozen tissue specimens and stained by an indirect immu-noperoxidase technique for hepatitis B surface antigen (HBsAg). Only 1 of 10 HBV DNA-positive samples contained HBsAg in the cytoplasm of tumor cells, although abundant HBsAg was present in adjacent normal cells in all 10 cases. There were no significant differences in histology between HCC that contained HBV DNA sequences and those that were virus negative. These data support the premise that HBV represents a major etiologic factor in the development of HCC in the Shanghai area of China, although the molecular basis of viral involvement remains obscure.
American Year-Book of Medicine and Surgery.
Journal: JAMA (1900)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Highlights of This Issue
Journal: Clinical Cancer Research (2016)

Metastatic castrate-resistant prostate cancer (mCRPC) is the most aggressive and incurable stage of the disease and the MYC oncogene is almost universally overexpressed in mCRPC. MYC directly enhances RNA polymerase I (Pol I) transcriptional activity but also regulates and cooperates with PIM kinases to accelerate tumorigenesis. Rebello and colleagues demonstrate the preclinical efficacy of targeted therapy against Pol I in combination with pan-PIM inhibition in genetically engineered mouse models and in patient-derived xenografts. This combination strategy shows promising efficacy in inhibiting MYC-driven prostate cancer and has implications for treating castrate resistant disease.Merkel cell carcinoma (MCC) is an aggressive cancer with frequent metastasis and death with few effective therapies. In this study, Feldmeyer and colleagues performed immune profiling of T-cell infiltration and PD-1/PD-L1 expression in primary MCC and related them to patient outcomes and Merkel cell polyomavirus (MCPyV) status. CD3+ and CD8+ T-cell density at the tumor periphery associated with improved overall survival for MCPyV+ MCC. The findings provide a potential biomarker for risk stratification and prognosis for MCC and a rationale to use immune checkpoint inhibitor therapy.Anaplasia in Wilms tumor has been associated with TP53 mutations. Ooms and colleagues show that 41% of prospectively identified diffuse anaplastic Wilms tumor (DAWT) tissue lacks TP53 abnormalities. TP53 wild type expression was associated with no or a very low volume of anaplastic cells in the tumor and significantly lowered the relapse rate. There may be a subset of DAWT patients without TP53 abnormalities that do better and may require less-intensive toxic therapy in some children.F. nucleatum primarily inhabits the oral cavity and can cause periodontal disease. Yamamura and colleagues demonstrate the presence of F. nucleatum in esophageal cancer tissue that was associated with tumor stage and poor prognosis. They additionally show a correlation with F. nucleatum and aggressive tumor behavior through activation of chemokines like CCL20. The data suggest that F. nucleatum could be used as a prognostic biomarker for esophageal cancer.
Implementing the Report of the Citizens Commission on Graduate Medical Education
Authors: James W. Haviland
Journal: JAMA (1969)

In late 1962 when the Board of Trustees of the American Medical Association asked the Citizens (Millis) Commission to study the problem of graduate education for physicians, it was in recognition of the need to make a broad and forwardlooking appraisal of the field with an eye to recommending apropriate and necessary changes. The extent of the proposed appraisal is best told by the following quotation from the specific charge to the commission, which was to make: (1) A determination of the various kinds of professional medical careers necessary to provide... society with medical services of a quality limited only by available knowledge. To the extent it is feasible, this would include an estimation of the quantitative distribution of the differing medical talents within the medical profession as a whole. (2) A definition of the general and specific characteristics of educational programs beyond medical school which will most effectively provide